The proposed experiments test the hypothesis that neuroanatomical changes seen in particular areas of the brains of chronic alcoholics are due specifically to the effects of alcohol ingestion. In order to control for such factors as alcohol intake, total caloric intake, nutritional balance and heredity, a rat animal model of chronic ethanol treatment will be used. The proposed experiments are related to two broad issues: 1) the regional selectivity of alcohol's effect on the brain, specifically neuroanatomical changes occurring as a result of chronic ethanol ingestion; 2) the result of such changes in one brain area on its connections with other brain areas. This study focuses on the mammillary bodies (MB), mediodorsal thalamic nucleus (MD), and prefrontal cortex (PFC), since the available evidence indicates that these areas are particularly affected in human chronic alcoholics. Blind animal coding procedures and quantitative computer-assisted image analysis techniques will be used to gather and analyze data concerning intrinsic and extrinsic changes in the neuroanatomy of the above three areas. Intrinsic changes to be examined (using cresyl violet, myelin and silver stains) include cell body and axonal fiber loss in particular subdivision of MB, segments of MD, and areas of PFC. These parcellations are significant since they relate to afferent and efferent connection patterns. Extrinsic changes to be examined (using autoradiographic tract-tracing techniques) include projections from MD to PFC, input to MB from the subicular region of the hippocampal formation, efferents of MB to the anterior thalamic nuclei, and input to MD from olfactory cortex. By first determining the precise nature and regional specificity of alcohol's effect on neuronal morphology and connections, one can then generate meaningful hypotheses regarding the mechanisms by which such effects occur.